Cystinuria
From The Cure For The Needy
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Cystinuria
Background
From eMedicine Urology
Cystinuria is an autosomal-recessive defect in reabsorptive transport of cystine and the dibasic amino acids ornithine, arginine, and lysine from the luminal fluid of the renal proximal tubule and small intestine. The only phenotypic manifestation of cystinuria is cystine urolithiasis, which often recurs throughout an affected individual’s lifetime. Surgical intervention is necessary, but the cornerstones of treatment are dietary and medical prevention of recurrent stone formation.
In 1810, Wollaston first described a different type of urinary calculi from the urinary bladder and coined the term cystic oxide.1 Berzelius recognized that the compound was not an oxide, and he named it cystine because the material originated from the bladder.2 In 1908, Sir Archibald Garrod identified cystinuria as one of the original "inborn errors of metabolism."3 Yeh et al4 and Dent and Rose5 showed abnormal excretion of the dibasic amino acids lysine, arginine, and ornithine in persons with cystinuria. In 1955, Harris et al reported the complex autosomal-recessive pattern of inheritance of cystinuria.6 In 1961, Milne et al demonstrated reduced intestinal absorption of dibasic amino acids in persons with cystinuria.7
In 1954, while studying skin sensitivity to penicillin and its derivatives, Tabachnick et al noted that one of the degradation products of penicillin, penicillamine, reacted with cystine to form a mixed disulfide, penicillamine cysteine.8 In 1963, Crawhall et al first used penicillamine to treat patients with cystinuria.9
In recent years, understanding of the genetic and molecular components of cystinuria has advanced. In 1993, Lee et al cloned a human cDNA (rBAT [renal basic amino acid transporter]) in chromosome 2, encoding a transport protein for cystine and dibasic amino acids.10 In 1997, Bisceglia et al identified type III cystinuria on band 19q13.1.11